Out of Africa: Stomach Ulcer Bug Migrated with Humans 60,000 Years Ago

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In 1985 Australian microbiologist Barry Marshall gobbled a petri dish full of Helicobacter pylori to prove to the world that the bacteria, rather than stress and spicy foods, were the primary cause of stomach ulcers. Two decades later his recklessness was honored with the Nobel Prize in Physiology or Medicine, which he shared with his colleague J. Robin Warren.

In light of a new study, published in this week's issue of Nature, it is odd that it took so long to finger H. pylori as the source of bouts of abdominal pain, nausea and hemorrhagic vomiting. According to the new work, the pathogen has infected humans for over 60,000 years and its genetic transformation over that time is remarkably similar to that of manmaking it a reasonable model for human migration and diversification.

"Like a trail of crumbs, the DNA of our Helicobacter pylori can show where we were born and where our ancestors traveled from over the past 60,000 years," says Marshall, a senior principal research fellow at the University of Western Australia. (Marshall was not involved in the Nature study.)

According to a 2002 study (published in the New England Journal of Medicine), H. pylori infects 50 percent of the global population. The helical bacterium is the only known microorganism that can survive in the highly acidic mucus lining of the stomach and duodenum, and it is now thought to be the cause of most stomach ulcers and gastritis, an irritation or inflammation of the stomach lining. It is also a risk factor for stomach cancer.

The current study was conducted by an international group of scientists led by University of Cambridge population geneticist Fran¿ois Balloux and Mark Achtman, a microbiologist at the Max Planck Institute for Biological Infections in Berlin. The work began, according to Balloux, when the pair decided to combine their data sets on human populations and pathogens to see if they could determine "when Helicobacter pylori first infected humans and [if this could] shed light on when and how anatomically modern humans colonized the world."

Human populations were broken down by geographic area, moving out of East Africa, believed to be the cradle of human civilization, and into western Europe, eastern Asia and southern Africa. The H. pylori strains used were similarly split into geographic regions: one set for Europe, two for Asia and three for Africa. While comparing DNA sequence patterns, the researchers noticed several similarities between the data sets: When plotting human genetic variation against that of the microbe, the researchers found that 73 percent of the DNA differences within a region could be explained by differences in H. pylori in the same population. In addition, the team found that H. pylori populations become more isolated as they move farther from East Africa, differing less genetically within the population, but more compared with East African populationsa finding that also held for human DNA.

Upon further analysis, researchers were able to estimate that the pathogen emerged from East Africanot China and southern Africa as previously surmisedbetween 54,500 and 61,500 years ago. A previous study on human settlement, led by Balloux, estimated human emergence from the same locale to have occurred 51,500 to 61,500 years ago.

In addition, the team focused on the microcosm of Europe. They showed that the pathogen was also a viable local model by noting that its pattern of population change on the continent suggested mixing from different geographic sources. This finding is backed by the literature on human migration, which argues that farmers in the Neolithic period moved into Europe from northern Africa and central Asia.

Marshall says molecular epidemiology"looking at statistical relationships between bacteria from different races"marks an improvement over studying human migration via ancient human DNA, which degrades if it is more than a few thousand years old. "At present, this is all rather new and the 'clock' has not been calibrated very exactly," he says, "but it is an exciting and fruitful area of new research."

Douglas Berg, a microbiologist at Washington University in St. Louis, while impressed by the new study, cautions, "Critical tests and rigorous proofs are difficult to obtain in their field of 'microbial anthropology,' and some scientists will think that the authors rather overstated their case."

Balloux says that each of the 16 authors on the current paper will likely have a different idea for the way this new model can be used. For his part, he says that studying H. pylori may allow scientists to circumvent mistrust of their research by certain ethnic groups, particularly Native Americans and Aborigines in Australia, who may be reluctant to provide blood or saliva samples. "The same people may be more willing to have their pathogens analyzed," he notes. "Future studies on H. pylori may [then] shed light on the colonization of Australia and the Americas."